tbuckley/cabot-search huggingface dataset:
Allogeneic CAR T Cells Targeting DLL3 Are Efficacious and Safe in Preclinical Models of Small Cell Lung Cancer
Authors: Yi Zhang, Silvia K. Tacheva-Grigorova, Janette Sutton, Zea Melton, Yvonne S.L. Mak, Cecilia Lay, Bryan A. Smith, Tao Sai, Thomas Van Blarcom, Barbra J. Sasu, Siler H. Panowski
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options. Delta-like ligand 3 (DLL3) is highly expressed on SCLC and several other types of neuroendocrine cancers, with limited normal tissue RNA expression in brain, pituitary, and testis, making it a promising CAR T-cell target for SCLC and other solid tumor indications. Experimental Design: A large panel of anti-DLL3 scFv-based CARs were characterized for both in vitro and in vivo activity. To understand the potential for pituitary and brain toxicity, subcutaneous or intracranial tumors expressing DLL3 were implanted in mice and treated with mouse cross-reactive DLL3 CAR T cells. Results: A subset of CARs demonstrated high sensitivity for targets with low DLL3 density and long-term killing potential in vitro. Infusion of DLL3 CAR T cells led to robust antitumor efficacy, including complete responses, in subcutaneous and systemic SCLC in vivo models. CAR T-cell infiltration into intermediate and posterior pituitary was detected, but no tissue damage in brain or pituitary was observed, and the hormone-secretion function of the pituitary was not ablated. Conclusions: In summary, the preclinical efficacy and safety data presented here support further evaluation of DLL3 CAR T cells as potential clinical candidates for the treatment of SCLC.
<scp>BTKi</scp> bonanza in <scp>CLL</scp>/<scp>SLL</scp>: Sorting out the differences
Authors: Paul J. Hampel, Sameer A. Parikh
Journal: American Journal of Hematology (2023)

PJH has no disclosures. SAP: Research funding has been provided to the institution from Janssen, AstraZeneca, Merck, and Genentech for clinical studies in which Sameer A. Parikh is a principal investigator. Honoraria has been provided to the institution from Pharmacyclics, Merck, AstraZeneca, Janssen, Genentech, Amgen, TG Therapeutics, Novalgen Limited, Kite Pharma, and AbbVie for Sameer A. Parikh's participation in consulting activities/advisory board meetings. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Much Ado about ASPS: The Rapidly Changing Treatment Paradigms of 2022
Authors: Breelyn A. Wilky, Alessandra Maleddu
Journal: Clinical Cancer Research (2023)

Summary A recent randomized phase II study of sunitinib or cediranib in alveolar soft part sarcoma established benchmark activity for commonly used tyrosine kinase inhibitors (TKI). The impact of TKIs, as well as immunotherapy, has redefined treatment paradigms and greatly improved outcomes for this historically dismal sarcoma. See related article by Nguyen et al., p. 1200
CMS Recommends Standardizing “Health Care Attachments”
Authors: Melissa Suran
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Novel Oral Polio Vaccine Safely Induces Antibodies Among Vaccine-Naive Infants
Authors: Anita Slomski
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
School-age outcomes among IVF-conceived children: A population-wide cohort study
Authors: Amber L. Kennedy, Beverley J. Vollenhoven, Richard J. Hiscock, Catharyn J. Stern, Susan P. Walker, Jeanie L. Y. Cheong, Jon L. Quach, Roxanne Hastie, David Wilkinson, John McBain, Lyle C. Gurrin, Vivien MacLachlan, Franca Agresta, Susan P. Baohm, Stephen Tong, Anthea C. Lindquist
Journal: PLoS Medicine (2023)

In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception.
Remote-controllable dosage management through a wearable iontophoretic patch utilizing a cell phone
Authors: Kenji Mori, Kotomi Yamazaki, Chihiro Takei, Takeshi Oshizaka, Issei Takeuchi, Kunio Miyaji, Hiroaki Todo, Shoko Itakura, Kenji Sugibayashi
Journal: Journal of Controlled Release (2023)
Trauma Activation Fees—A Fair Approach to Reimburse Trauma Readiness Costs or a Pathway to Profitability?
Authors: Lisa M. Knowlton, Elliott R. Haut
Journal: JAMA Network Open (2023)

Hospitals providing specialized trauma care incur substantial readiness costs associated with being able to provide round-the-clock emergency services-24 hours a day, every day of the year.The components of trauma readiness, including administrative and clinical staffing, in-house operating rooms, blood banks, and educational and community outreach, are described in the American College of Surgeons (ACS) Resources for Optimal Care of the Injured Patient. 1 Previous work by Ashley et al 2 estimated the mean cost of trauma readiness as $6 million to $10 million annually among level I trauma centers.Trauma activation fees were created in 2002 to recuperate some of these readiness costs, which had previously never been covered by charges to individual patients.The fees can offset costs such as administrative fees, trauma team member salaries, equipment, supplies, physician trauma coverage agreements, trauma medical director and trauma registrar time, operating room readiness, blood product availability, education, protocol development, and local county emergency medical services fees.There is currently no standard fee schedule or uniform approach to calculating trauma
Low-Carbohydrate, High-Fat Diet Improved Type 2 Diabetes Without Restricting Calories
Authors: Anita Slomski
Journal: JAMA (2023)

People with type 2 diabetes who ate a low-carbohydrate, high-fat (LCHF) diet for 6 months had better glycemic control than those who ate a high-carbohydrate, low-fat (HCLF) diet, a recent trial reported, but the differences weren’t sustainable 3 months after the intervention.
Glutamine‐Based Metabolism Normalization and Oxidative Stress Alleviation by Self‐Assembled Bilirubin/V9302 Nanoparticles for Psoriasis Treatment
Authors: Xinyu Jiang, Shuqi Huang, Wenjing Cai, Peiqi Wang, Zewei Jiang, Minghui Wang, Linyi Zhang, Pengfei Mao, Lijia Chen, Ruizhen Wang, Tuyue Sun, Yiling Jiang, Qing Yao, Ruijie Chen, Longfa Kou
Journal: Advanced Healthcare Materials (2023)

Abstract Psoriasis is an immune‐mediated chronic inflammatory skin disorder characterized by epidermal hyperplasia and infiltration of inflammatory cells. Even though the pathogenesis remains unclear, T helper 17 (Th17) cells‐mediated inflammation and keratinocyte‐involved proliferation are considered to play key roles during the occurrence and the development of psoriasis. Therefore, suppressing the infiltration/function of Th17 and the abnormal hyperplasia of keratinocytes can be a rational strategy for ameliorating and treating psoriasis. In this study, a self‐assembly nanoparticle (BVn) is developed with bilirubin (an endogenous antioxidant) and V9302 (a blocker of ASCT2, an amino acid transporter mediating glutamine influx for providing energy and activating mammalian target of rapamycin [mTOR] pathway) to intervene the local metabolism and alleviate oxidative stress for psoriasis treatment. BVn effectively suppresses inflammatory keratinocyte proliferation and scavenges excess reactive oxygen species (ROS). In the in vivo psoriasis mouse model, BVn shows increased permeation and delayed retention in the psoriatic lesion and reverses the psoriasis‐related symptoms, evidenced by the normalized keratinocyte condition and decreased Th17 infiltration/activation. Mechanism study indicates that BVn not only cut off the energy supply but also suppressed cell proliferation or lymph cell expansion by deactivating mTOR pathway, besides alleviated oxidative stress. BVn‐based glutamine metabolism modulation strategy offers a promising strategy for psoriasis therapy.
Improvements in Adverse Event Rates Among Hospitalized Patients—Reply
Authors: William V. Padula, Peter J. Pronovost
Journal: JAMA (2023)

In Reply “The goal is zero harms” has resonated throughout patient safety. Two decades after To Err Is Human, health care continues to face recurrences of a multitude of preventable adverse events. No guideline, policy, or public health intervention has been able to eliminate adverse events.
Concomitant latent pulmonary vascular disease leads to impaired global cardiac performance in heart failure with preserved ejection fraction
Authors: Andreas Schuster, Alexander Schulz, Torben Lange, Ruben Evertz, Finn Hartmann, Johannes T. Kowallick, Kristian Hellenkamp, Martin Uecker, Tim Seidler, Gerd Hasenfuß, Sören J. Backhaus
Journal: European Journal of Heart Failure (2023)

ABSTRACT Aims The REDUCE‐LAP II trial demonstrated adverse outcomes after interatrial shunt device (IASD) placement in heart failure with preserved ejection fraction (HFpEF) attributed to latent pulmonary vascular disease (PVD). We hypothesized that exercise stress cardiovascular magnetic resonance (CMR) imaging could provide non‐invasive characterization of cardiac and pulmonary physiology for improved patient selection. Methods and results The HFpEF‐Stress trial prospectively enrolled 75 patients with exertional dyspnoea and diastolic dysfunction. Patients underwent rest and exercise stress right heart catheterization, echocardiography and CMR imaging. Pulmonary artery and capillary wedge pressures, cardiac index (CI) and pulmonary vascular resistance (PVR) were calculated. Latent PVD was defined as increased PVR ≥ 1.74 Wood units during exercise stress. CMR assessed long‐axis strains (LAS) and filling volumes of all cardiac chambers. Right ventricular (RV) function was further quantified by stroke and peak flow volumes. Patients with latent PVD ( n = 24) showed lower RV function (rest tricuspid annular plane systolic excursion, p = 0.010; stress RV LAS, p &lt; 0.001) compared to patients without ( n = 43). During exercise stress, RV stroke and peak flow volumes ( p &lt; 0.001) were reduced and led to impaired left atrial filling ( p = 0.040) with a strong statistical trend to impaired ventricular (LV) filling ( p = 0.098). This subsequently resulted in reduced LV‐CI ( p &lt; 0.001) despite preserved LV systolic function (LV LAS p ≥ 0.255). The degree of RV dysfunction during exercise stress best predicted latent PVD (RV peak flow, area under the curve at rest 0.73 vs. stress 0.89, p = 0.004). Conclusions Latent PVD is a feature of HFpEF and is associated with impaired RV functional reserve, global diastolic filling and LV‐CI. This can be quantified by CMR and used to identify patients likely to benefit from IASD implantation.
Acute appendicitis manifests as two microbiome state types with oral pathogens influencing severity
Authors: Marcus Blohs, Alexander Mahnert, Kevin Brunnader, Christina Flucher, Christoph Castellani, Holger Till, Georg Singer, Christine Moissl-Eichinger
Journal: Gut Microbes (2023)

Mounting evidence suggests that acute appendicitis (AA) is not one but two diseases: complicated appendicitis, which is associated with necrosis leading to perforation or periappendicular abscess, and uncomplicated appendicitis, which does not necessarily result in perforation. Even though AA is the most frequent cause of surgery from abdominal pain, little is known about the origins and etiopathogenesis of this disease, much less regarding the different disease types. In this study, we investigated the microbiome (inter-domain amplicon and metagenome sequencing) of samples from the appendix, rectum and peritoneum of 60 children and adolescents with AA to assess the composition and potential function of bacteria, archaea and fungi. The analysis of the appendix microbial community revealed a shift depending on the severity of the AA. This shift was reflected by two major community state types that represented the complicated and uncomplicated cases. We could demonstrate that complicated, but not uncomplicated, appendicitis is associated with a significant local expansion of oral, bacterial pathogens in the appendix, most strongly influenced by necrotizing Fusobacterium spp., Porphyromonas and Parvimonas. Uncomplicated appendicitis, however, was characterized by gut-associated microbiomes. Our findings support the hypothesis that two disease types exist in AA, which cannot be distinguished beyond doubt using standard clinical characterization methods or by analysis of the patient's rectal microbiome. An advanced microbiome diagnosis, however, could improve non-surgical treatment of uncomplicated AA.
Interleukin-6 Receptor Polymorphism Attenuates Clonal Hematopoiesis-Mediated Coronary Artery Disease Risk Among 451 180 Individuals in the UK Biobank
Authors: Caitlyn Vlasschaert, J. Brett Heimlich, Michael J. Rauh, Pradeep Natarajan, Alexander G. Bick
Journal: Circulation (2023)

IL6 Modulates CHIP/CAD Risk in Full UK Biobank Figure.Genetic attenuation of IL6R signaling is protective against CHIP-associated CAD risk in the UK Biobank 450 000-person data set when high-confidence CHIP calls are used.A, Associations between clonal hematopoiesis of indeterminate potential (CHIP) with increasing numbers of next-generation sequencing reads that support the CHIP variant and age (top) and TERT genetic variant rs7705526 (middle), assessed with a logistic regression with binary CHIP status as the outcome.The rs7705526 genotype was coded with an additive model.Odds ratios (ORs) represent per-unit SD increase in the predictor variable.Bottom, Total number of individuals putatively identified with CHIP at each of these thresholds.Five supporting reads was the optimal balance of sensitivity and specificity based on associations with age and TERT genetic variant.B, Cumulative incidence of coronary artery disease (CAD) by CHIP status, defined with at least 5 supporting reads.C, When CHIP is defined with at least 5 supporting reads, CHIP is associated with incident CAD, and IL6R p.Asp358Ala single nucleotide polymorphism (SNP) is protective against this risk.This association is observed for non-DNMT3A CHIP and CHIP with a large variant allele frequency (≥10%) but not DNMT3A-CHIP.D, When CHIP is defined with a relaxed criteria of only 3 supporting reads, the association of CHIP with incident CAD is greatly attenuated, and IL6R p.Asp358Ala SNP is not protective.IL6R indicates interleukin-6 receptor.
Antibody–Exatecan Conjugates with a Novel Self-immolative Moiety Overcome Resistance in Colon and Lung Cancer
Authors: Weining Weng, Tao Meng, Qianqian Zhao, Yi Shen, Guoxiang Fu, Jing Shi, Yue Zhang, Zhaohui Wang, Mingqiao Wang, Rong Pan, Linjie Ma, Caiwei Chen, Lijun Wang, Biao Zhou, Hui Zhang, Junyi Pu, Jianjian Zhang, Yi Peter Hu, Guoqiang Hua, Yu Qian, Shu-Hui Liu, Wenhao Hu, Xun Meng
Journal: Cancer Discovery (2023)

Antibody-drug conjugates (ADC) using DNA topoisomerase I inhibitor DXd/SN-38 have transformed cancer treatment, yet more effective ADCs are needed for overcoming resistance. We have designed an ADC class using a novel self-immolative T moiety for traceless conjugation and release of exatecan, a more potent topoisomerase I inhibitor with less sensitivity to multidrug resistance (MDR). Characterized by enhanced therapeutic indices, higher stability, and improved intratumoral pharmacodynamic response, antibody-T moiety-exatecan conjugates targeting HER2, HER3, and TROP2 overcome the intrinsic or treatment resistance of equivalent DXd/SN-38 ADCs in low-target-expression, large, and MDR+ tumors. T moiety-exatecan ADCs display durable antitumor activity in patient-derived xenograft and organoid models representative of unmet clinical needs, including EGFR ex19del/T790M/C797S triple-mutation lung cancer and BRAF/KRAS-TP53 double-mutant colon cancer, and show synergy with PARP/ATR inhibitor and anti-PD-1 treatment. High tolerability of the T moiety-exatecan ADC class in nonhuman primates supports its potential to expand the responding patient population and tumor types beyond current ADCs. ADCs combining a novel self-immolative moiety and topoisomerase I inhibitor exatecan as payload show deep and durable response in low-target-expressing and MDR+ tumors resistant to DXd/SN-38 ADCs without increasing toxicity. This new class of ADCs has the potential to benefit an additional patient population beyond current options. See related commentary by Gupta et al., p. 817. This article is highlighted in the In This Issue feature, p. 799.
US Life Expectancy in 2021 Lowest Since 1996
Authors: Bridget M. Kuehn
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The State of the US Public Health Workforce: Ongoing Challenges and Future Directions
Authors: Jonathon P. Leider, Valerie A. Yeager, Chelsey Kirkland, Heather Krasna, Rachel Hare Bork, Beth Resnick
Journal: Annual Review of Public Health (2023)

Between the 2009 Great Recession and the onset of the COVID-19 pandemic, the US state and local governmental public health workforce lost 40,000 jobs. Tens of thousands of workers also left during the pandemic and continue to leave. As governmental health departments are now receiving multimillion-dollar, temporary federal investments to replenish their workforce, this review synthesizes the evidence regarding major challenges that preceded the pandemic and remain now. These include the lack of the field's ability to readily enumerate and define the governmental public health workforce as well as challenges with the recruitment and retention of public health workers. This review finds that many workforce-related challenges identified more than 20 years ago persist in the field today. Thus, it is critical that we look back to be able to then move forward to successfully rebuild the workforce and assure adequate capacity to protect the public's health and respond to public health emergencies.
Letter by Gutmann et al Regarding Article, “Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles”
Authors: Clemens Gutmann, Stefan Stojkovic, Manuel Mayr
Journal: Circulation (2023)
Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia
Authors: Iiris Nyholm, Maria Hukkinen, Marjut Pihlajoki, Joseph R. Davidson, Athanasios Tyraskis, Jouko Lohi, Päivi Heikkilä, Satu Hänninen, Noora Andersson, Katja Eloranta, Olli Carpén, Markku Heikinheimo, Mark Davenport, Mikko P. Pakarinen
Journal: Hepatology (2023)

Background and Aims: Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. Approach and Results: Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19 , and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61 pg/mL, p &lt;0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145 pg/mL, p =0.047), and those subsequently underwent liver transplantation (410 vs. 99 pg/mL, p =0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 &lt;109 pg/mL predicted native liver survival (HR: 4.31, p &lt;0.001) also among patients operated &lt;60 days of age (HR: 8.77, p =0.004) or after successful KPE (HR: 6.76, p =0.01). Serum FGF19 correlated positively with increased serum primary bile acids ( R =0.41, p =0.004) and ductular reaction ( R =0.39, p =0.004). Conclusions: Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction.